Our long-range goal is to understand mechanisms of negative regulation of transcription of eukaryotic genes. Our experiments will be performed in yeast, drosophila and in mammalian cells. We will isolate and analyze new negative regulators that work "at a distance"; these negative regulators bear "repressing regions" fused to a DNA-binding fragment. We will study the mechanism by which the yeast negative regulators GAL80 inhibits activation by the yeast transcriptional activator GAL4, and we will study the effects of galactose (an inducer) on GAL80 action. We will analyze the ability of the yeast protein MCM1 to interact with either of two partners - 1 or 2 - to produce in one case a repressing and in the other case an activating complex, and we will attempt to isolate mammalian homologues of yeast proteins required for repression by MCM1/2.